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World Journal of Diabetes Mar 2024Gestational diabetes mellitus (GDM) is a pregnancy-related complication characterized by abnormal glucose metabolism in pregnant women and has an important impact on... (Review)
Review
Gestational diabetes mellitus (GDM) is a pregnancy-related complication characterized by abnormal glucose metabolism in pregnant women and has an important impact on fetal development. As a bridge between the mother and the fetus, the placenta has nutrient transport functions, endocrine functions, , and can regulate placental nutrient transport and fetal growth and development according to maternal metabolic status. Only by means of placental transmission can changes in maternal hyperglycemia affect the fetus. There are many reports on the placental pathophysiological changes associated with GDM, the impacts of GDM on the growth and development of offspring, and the prevalence of GDM in offspring after birth. Placental epigenetic changes in GDM are involved in the programming of fetal development and are involved in the pathogenesis of later chronic diseases. This paper summarizes the effects of changes in placental nutrient transport function and hormone secretion levels due to maternal hyperglycemia and hyperinsulinemia on the development of offspring as well as the participation of changes in placental epigenetic modifications due to maternal hyperglycemia in intrauterine fetal programming to promote a comprehensive understanding of the impacts of placental epigenetic modifications on the development of offspring from patients with GDM.
PubMed: 38591094
DOI: 10.4239/wjd.v15.i3.378 -
BMJ Case Reports Apr 2024The ampulla portion of the fallopian tube is the most common site of ectopic pregnancy (70%), with approximately 2% of pregnancies implanted in the interstitial portion....
The ampulla portion of the fallopian tube is the most common site of ectopic pregnancy (70%), with approximately 2% of pregnancies implanted in the interstitial portion. In general, an interstitial ectopic pregnancy (IEP) is difficult to diagnose and is associated with a high rate of complications-most patients with an IEP present with severe abdominal pain and haemorrhagic shock due to an ectopic rupture. Chronic tubal pregnancy (CTP) is an uncommon condition with an incidence of 20%. The CTP has a longer clinical course and a negative or low level of serum beta-human chorionic gonadotropin due to perished chorionic villi. This study presents a case of a woman who was diagnosed with a chronic IEP (CIEP) which was successfully treated by surgery. This case also acts as a cautionary reminder of considering a CIEP in women of reproductive age presenting with amenorrhea, vaginal bleeding and a negative pregnancy test.
Topics: Pregnancy; Humans; Female; Pregnancy, Ectopic; Chorionic Gonadotropin, beta Subunit, Human; Fallopian Tubes; Pregnancy Tests; Abdominal Pain; Pregnancy, Tubal
PubMed: 38589241
DOI: 10.1136/bcr-2023-259267 -
JBMR Plus May 2024Calcitriol circulates at low levels in normal human and rodent fetuses, in part due to increased 24-hydroxylation of calcitriol and 25-hydroxyvitamin D by 24-hydroxylase...
Calcitriol circulates at low levels in normal human and rodent fetuses, in part due to increased 24-hydroxylation of calcitriol and 25-hydroxyvitamin D by 24-hydroxylase (CYP24A1). Inactivating mutations of cause high postnatal levels of calcitriol and the human condition of infantile hypercalcemia type 1, but whether the fetus is disturbed by the loss of CYP24A1 is unknown. We hypothesized that loss of in fetal mice will cause high calcitriol, hypercalcemia, and increased placental calcium transport. The mice were mated to create pregnancies with wildtype, , and null fetuses. The null fetuses were hypercalcemic, modestly hypophosphatemic (compared to fetuses only), with 3.5-fold increased calcitriol, 4-fold increased fibroblast growth factor 23 (FGF23), and unchanged parathyroid hormone. The quantitative RT-PCR confirmed the absence of and 2-fold increases in , sodium-calcium exchanger type 1, and calcium-sensing receptor in null placentas but not in fetal kidneys; these changes predicted an increase in placental calcium transport. However, placental Ca and P transport were unchanged in null fetuses. Fetal ash weight and mineral content, placental weight, crown-rump length, and skeletal morphology did not differ among the genotypes. Serum procollagen 1 intact N-terminal propeptide and bone expression of sclerostin and were reduced while calcitonin receptor was increased in nulls. In conclusion, loss of in fetal mice causes hypercalcemia, modest hypophosphatemia, and increased FGF23, but no alteration in skeletal development. Reduced incorporation of calcium into bone may contribute to the hypercalcemia without causing a detectable decrease in the skeletal mineral content. The results predict that human fetuses bearing homozygous or compound heterozygous inactivating mutations of will also be hypercalcemic in utero but with normal skeletal development.
PubMed: 38577520
DOI: 10.1093/jbmrpl/ziae012 -
Reproductive Biology and Endocrinology... Apr 2024Inadequate endometrial receptivity often results in embryo implantation failure and miscarriage. Human chorionic gonadotropin (hCG) is a key signaling molecule secreted...
Inadequate endometrial receptivity often results in embryo implantation failure and miscarriage. Human chorionic gonadotropin (hCG) is a key signaling molecule secreted during early embryonic development, which regulates embryonic maternal interface signaling and promotes embryo implantation. This study aimed to examine the impact of hCG on endometrial receptivity and its underlying mechanisms. An exploratory study was designed, and endometrial samples were obtained from women diagnosed with simple tubal infertility or male factor infertile (n = 12) and recurrent implantation failure (RIF, n = 10). Using reverse transcription-quantitative PCR and western blotting, luteinizing hormone (LH)/hCG receptor (LHCGR) levels and autophagy were detected in the endometrial tissues. Subsequently, primary endometrial stromal cells (ESCs) were isolated from these control groups and treated with hCG to examine the presence of LHCGR and markers of endometrial receptivity (HOXA10, ITGB3, FOXO1, LIF, and L-selectin ligand) and autophagy-related factors (Beclin1, LC3, and P62). The findings revealed that the expressions of receptivity factors, LHCGR, and LC3 were reduced in the endometrial tissues of women with RIF compared with the control group, whereas the expression of P62 was elevated. The administration of hCG to ESCs specifically activated LHCGR, stimulating an increase in the endometrial production of HOXA10, ITGB3, FOXO1, LIF and L-selectin ligands. Furthermore, when ESCs were exposed to 0.1 IU/mL hCG for 72 h, the autophagy factors Beclin1 and LC3 increased within the cells and P62 decreased. Moreover, the apoptotic factor Bax increased and Bcl-2 declined. However, when small interfering RNA was used to knock down LHCGR, hCG was less capable of controlling endometrial receptivity and autophagy molecules in ESCs. In addition, hCG stimulation enhanced the phosphorylation of ERK1/2 and mTOR proteins. These results suggest that women with RIF exhibit lower levels of LHCGR and compromised autophagy function in their endometrial tissues. Thus, hCG/LHCGR could potentially improve endometrial receptivity by modulating autophagy and apoptosis.
Topics: Pregnancy; Humans; Male; Female; Beclin-1; L-Selectin; Endometrium; Chorionic Gonadotropin; Embryo Implantation; Autophagy; Stromal Cells; Apoptosis
PubMed: 38576003
DOI: 10.1186/s12958-024-01205-x -
In Vitro Cellular & Developmental... Apr 2024It has been reported that the effective inhibition of vascular endothelial growth factor (VEGF) can prevent the progression of ovarian hyperstimulation syndrome (OHSS)....
It has been reported that the effective inhibition of vascular endothelial growth factor (VEGF) can prevent the progression of ovarian hyperstimulation syndrome (OHSS). The present study aimed to investigate the mechanism underlying the effect of vitamin D (VD3) on OHSS in mouse models and granulosa cells. The effects of VD3 administration (16 and 24 IU) on ovarian permeability were determined using Evans blue. In addition, ovarian pathology, corpus luteum count, inflammatory responses, and hormone and VEGFA levels were assessed using pathological sections and ELISA. Molecular docking predicted that pentraxin 3 (PTX3) could be a potential target of VD3, and therefore, the effects of human chorionic gonadotropin (hCG) and VD3 as well as PTX3 overexpression on the production and secretion of VEGFA in granulosa cells were also investigated using western blotting and immunofluorescence. Twenty-four IU VD3 significantly reversed the increase in ovarian weight and permeability in mice with OHSS. Additionally, VD3 diminished congestion and the number of corpus luteum in the ovaries and reduced the secretion levels of inflammatory factors and those of estrogen and progesterone. Notably, VD3 downregulated VEGFA and CD31 in ovarian tissues, while the expression levels of PTX3 varied among different groups. Furthermore, VD3 restored the hCG-induced enhanced VEGFA and PTX3 expression levels in granulosa cells, whereas PTX3 overexpression abrogated the VD3-mediated inhibition of VEGFA production and secretion. The present study demonstrated that VD3 could inhibit the release of VEGFA through PTX3, thus supporting the beneficial effects of VD3 administration on ameliorating OHSS symptoms.
Topics: Animals; Female; Humans; Mice; C-Reactive Protein; Cholecalciferol; Chorionic Gonadotropin; Granulosa Cells; Ovarian Hyperstimulation Syndrome; Ovary; Serum Amyloid P-Component; Vascular Endothelial Growth Factor A; Mice, Inbred ICR
PubMed: 38573397
DOI: 10.1007/s11626-024-00898-z -
Journal of Paediatrics and Child Health 2024Hormone replacement therapy with testosterone for pubertal induction in boys with congenital hypogonadotropic hypogonadism (CHH) achieves virilization but not...
Fertility outcomes in male adults with congenital hypogonadotropic hypogonadism treated during puberty with human chorionic gonadotropin and recombinant follicle stimulating hormone.
AIM
Hormone replacement therapy with testosterone for pubertal induction in boys with congenital hypogonadotropic hypogonadism (CHH) achieves virilization but not spermatogenesis. By contrast, human chorionic gonadotropin (hCG) and recombinant follicle stimulating hormone (rFSH) provides both virilization and spermatogenesis. Fertility outcomes of boys treated with recombinant therapy during adolescence have been infrequently described. We report fertility induction and pregnancy outcomes in CHH patients treated with recombinant gonadotropins during puberty.
METHODS
Data of six subjects with CHH (n = 3 Kallmann syndrome & n = 3 Isolated hypogonadotropic hypogonadism) treated with hCG and FSH for pubertal induction were reviewed. Of these, five underwent subsequent fertility induction while one desired fertility at the end of pubertal induction.
RESULTS
Partners of all subjects achieved pregnancies using hCG and rFSH, all with full term live births. All infants were clinically normal.
CONCLUSION
This study provides early evidence of proof of concept of use of gonadotropin induction of puberty being beneficial in subsequent fertility outcome.
Topics: Adult; Pregnancy; Infant; Female; Adolescent; Humans; Male; Chorionic Gonadotropin; Hypogonadism; Follicle Stimulating Hormone; Testosterone; Fertility; Recombinant Proteins; Puberty; Virilism
PubMed: 38572627
DOI: 10.1111/jpc.16540 -
Reproductive Biology and Endocrinology... Apr 2024Diminished ovarian reserve (DOR) is one of the obstacles affecting the reproductive outcomes of patients receiving assisted reproductive therapy. The purpose of this...
BACKGROUND
Diminished ovarian reserve (DOR) is one of the obstacles affecting the reproductive outcomes of patients receiving assisted reproductive therapy. The purpose of this study was to investigate whether dual trigger, including gonadotropin-releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG), can improve pregnancy outcomes in patients with DOR undergoing in vitro fertilization (IVF) cycles using mild stimulation protocols.
METHODS
A total of 734 patients with DOR were included in this retrospective study. Patients were divided into a recombinant hCG trigger group and a dual trigger group (hCG combined with GnRHa) according to the different trigger drugs used. The main outcome measures included the number of oocytes retrieved, the fertilization rate, the number of transferable embryos, the implantation rate, the clinical pregnancy rate, the miscarriage rate, the live birth rate (LBR), and the cumulative live birth rate (CLBR). Generalized linear model and logistic regression analyses were performed for confounding factors.
RESULTS
There were 337 cycles with a single hCG trigger and 397 cycles with dual trigger. The dual trigger group demonstrated significantly higher numbers of retrieved oocytes [3.60 vs. 2.39, adjusted β = 0.538 (0.221-0.855)], fertilized oocytes [2.55 vs. 1.94, adjusted β = 0.277 (0.031-0.523)] and transferable embryos [1.22 vs. 0.95, adjusted β = 0.162 (-0.005-0.329)] than did the hCG trigger group, whereas no significant difference in the fertilization rate was observed between the two groups. Moreover, the embryo transfer cancellation rate (35.5% vs. 43.9%) was obviously lower in the dual trigger group. Among the fresh embryo transfer cycles, the implantation rate, clinical pregnancy rate, miscarriage rate and live birth rate were similar between the two groups. After controlling for potential confounding variables, the trigger method was identified as an independent factor affecting the number of oocytes retrieved but had no significant impact on the CLBR.
CONCLUSIONS
Dual triggering of final oocyte maturation with hCG combined with GnRHa can significantly increase the number of oocytes retrieved in patients with DOR but has no improvement effect on the implantation rate, clinical pregnancy rate or LBR of fresh cycles or on the CLBR.
Topics: Pregnancy; Humans; Female; Chorionic Gonadotropin; Retrospective Studies; Abortion, Spontaneous; Ovarian Reserve; Ovulation Induction; Gonadotropin-Releasing Hormone; Fertilization in Vitro; Pregnancy Rate; Oocytes; Ovarian Diseases
PubMed: 38566172
DOI: 10.1186/s12958-024-01211-z -
Toxicology Letters May 2024Pentachlorophenol (PCP) is a widely used pesticide. However, whether PCP and its metabolite chloranil have endocrine-disrupting effects by inhibiting placental...
Pentachlorophenol (PCP) is a widely used pesticide. However, whether PCP and its metabolite chloranil have endocrine-disrupting effects by inhibiting placental 3β-hydroxysteroid dehydrogenase 1 (3β-HSD1) remains unclear. The study used in vitro assays with human and rat placental microsomes to measure 3β-HSD activity as well as human JAr cells to evaluate progesterone production. The results showed that PCP exhibited moderate inhibition of human 3β-HSD1, with an IC value of 29.83 μM and displayed mixed inhibition in terms of mode of action. Conversely, chloranil proved to be a potent inhibitor, demonstrating an IC value of 147 nM, and displaying a mixed mode of action. PCP significantly decreased progesterone production by JAr cells at 50 μM, while chloranil markedly reduced progesterone production at ≥1 μM. Interestingly, PCP and chloranil moderately inhibited rat placental homolog 3β-HSD4, with IC values of 27.94 and 23.42 μM, respectively. Dithiothreitol (DTT) alone significantly increased human 3β-HSD1 activity. Chloranil not PCP mediated inhibition of human 3β-HSD1 activity was completely reversed by DTT and that of rat 3β-HSD4 was partially reversed by DTT. Docking analysis revealed that both PCP and chloranil can bind to the catalytic domain of 3β-HSDs. The difference in the amino acid residue Cys83 in human 3β-HSD1 may explain why chloranil is a potent inhibitor through its interaction with the cysteine residue of human 3β-HSD1. In conclusion, PCP is metabolically activated to chloranil as a potent inhibitor of human 3β-HSD1.
Topics: Humans; Female; Rats; Pregnancy; Animals; Placenta; Pentachlorophenol; Chloranil; Progesterone; Activation, Metabolic; Models, Molecular; Hydroxysteroid Dehydrogenases; 3-Hydroxysteroid Dehydrogenases; 17-Hydroxysteroid Dehydrogenases
PubMed: 38555059
DOI: 10.1016/j.toxlet.2024.03.007 -
Journal of Medical Case Reports Mar 2024Choriocarcinoma is a rare and highly malignant form of gestational trophoblastic disease that may develop following pregnancy, abortion, or a hydatiform mole. Renal... (Review)
Review
BACKGROUND
Choriocarcinoma is a rare and highly malignant form of gestational trophoblastic disease that may develop following pregnancy, abortion, or a hydatiform mole. Renal metastatic involvement by post molar choriocarcinoma is even rarer. In this case report, we describe a unique case of post molar choriocarcinoma with a solitary renal metastasis in the absence of a primary uterine tumor and metastases in other sites, which presented with urological symptoms and spontaneous renal hemorrhage.
CASE PRESENTATION
A 41-year-old Persian woman with history of complete hydatiform mole presented with severe flank pain, nausea, vomiting, gross hematuria, and vaginal bleeding. Laboratory tests demonstrated a serum beta human chorionic gonadotropin hormone level of 60,000 mIU/mL. Imaging studies showed a lesion at the lower pole of the left kidney with active bleeding surrounded by hematoma, as well as an empty uterine cavity. Additionally, bilateral pleural effusion was detected without any lesion within the lungs. Subsequently, the patient underwent laparotomy, partial nephrectomy, and left para-ovarian cystectomy. Endometrial curettage was also carried out. The histopathology report revealed choriocarcinoma renal metastasis with high expression of beta human chorionic gonadotropin, cytokeratin 7, and Ki 67. Moreover, there were no malignant cells in the endometrial curettage specimens, and a corpus luteum cyst was found within the para-ovarian cyst. Further investigations revealed that the pleural effusion was free of malignant cells, and there was no evidence of metastatic lesions in the brain. As a result, the patient was referred to the oncology department to receive chemotherapy, and the beta human chorionic gonadotropin levels dropped to 5 mIU/mL after receiving courses of a standard regimen of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine/oncovin over 3 weeks. Finally, monthly measurements of beta human chorionic gonadotropin levels for 6 months indicated that levels have constantly remained within normal ranges, showing no evidence of recurrence or new metastasis.
CONCLUSIONS
Urological symptoms such as hematuria or spontaneous renal hemorrhage might be the only presentation of post molar choriocarcinoma with renal involvement. Thus, it can be beneficial to measure serum beta human chorionic gonadotropin levels among females of childbearing age who present with unexplained urological symptoms, especially if there is a history of prior hydatiform mole.
Topics: Adult; Female; Humans; Choriocarcinoma; Chorionic Gonadotropin, beta Subunit, Human; Hematuria; Hydatidiform Mole; Kidney Neoplasms; Pleural Effusion; Uterine Neoplasms; Vincristine
PubMed: 38553733
DOI: 10.1186/s13256-024-04464-9 -
European Journal of Obstetrics,... May 2024The M6 prediction model stratifies the risk of development of ectopic pregnancy (EP) for women with pregnancy of unknown location (PUL) into low risk or high risk, using...
OBJECTIVES
The M6 prediction model stratifies the risk of development of ectopic pregnancy (EP) for women with pregnancy of unknown location (PUL) into low risk or high risk, using human chorionic gonadotrophin (hCG) and progesterone levels at the initial visit to a gynaecological emergency room and hCG level at 48 h. This study evaluated a second model, the M6 model, which does not include the progesterone level at the initial visit. The main aim of this study was to validate the diagnostic accuracy of the M6 model in a population of French women.
STUDY DESIGN
Between January and December 2021, all women with an hCG measurement from the gynaecological emergency department of a teaching hospital were screened for inclusion in this study. Women with a pregnancy location determined before or at the second visit were excluded. The diagnostic test was based on logistic regression of the M6 model, with classification into two groups: high risk of EP (≥5%) and low risk of EP (<5%). The reference test was the final outcome based on clinical, biological and sonographic results: failed PUL (FPUL), intrauterine pregnancy (IUP) or EP. Diagnostic performance for risk prediction of EP, and also IUP and FPUL, was calculated.
RESULTS
In total, 759 women with possible PUL were identified. After screening, 341 women with PUL were included in the main analysis. Of these, 186 (54.5%) were classified as low risk, including three (1.6%) with a final outcome of EP. The remaining 155 women with PUL were classified as high risk, of whom 60 (38.7%), 66 (42.8%) and 29 (18.7%) had a final outcome of FPUL, IUP and EP, respectively. Of the 32 women with PUL with a final outcome of EP, 29 (90.6%) were classified as high risk and three (9.4%) were classified as low risk. Therefore, the performance of the M6 model to predict EP had a negative predictive value of 98.4%, a positive predictive value of 18.7%, sensitivity of 90.6% and specificity of 59.2%. If the prediction model had been used, it is estimated that 4.5 visits per patient could have been prevented.
CONCLUSION
The M6 model could be used safely in the French population for risk stratification of PUL. Its use in clinical practice should result in a substantial reduction in the number of visits to a gynaecological emergency room.
Topics: Pregnancy; Female; Humans; Pregnancy Outcome; Progesterone; Triage; Pregnancy, Ectopic; Chorionic Gonadotropin; Logistic Models
PubMed: 38552504
DOI: 10.1016/j.ejogrb.2024.03.010